Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes

Onengut‐Gumuscu, Suna; Webb‐Robertson, Bobbie‐Jo M.; Sarkar, Soumyadeep; Manichaikul, Ani; Hu, Xiaowei; Frazer‐Abel, Ashley; Holers, V. Michael; Rewers, Marian J.; Rich, Stephen S.

doi:10.1002/dmrr.3716

Diabetes Metabolism Res

2023

DOI: 10.1002/dmrr.3716

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Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes

Suna Onengut‐Gumuscu,

Bobbie‐Jo M. Webb‐Robertson,

Soumyadeep Sarkar

et al.

Abstract: Type 1 diabetes is an autoimmune disease in which one's own immune system destroys insulin‐secreting beta cells in the pancreas. This process results in life‐long dependence on exogenous insulin for survival. Both genetic and environmental factors play a role in disease initiation, progression, and ultimate clinical diagnosis of type 1 diabetes. This review will provide background on the natural history of type 1 diabetes and the role of genetic factors involved in the complement system, as several recent stud… Show more

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Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Chen,

Guo,

2023

Hum Genomics

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Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.

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Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Chen,

Guo,

2023

Hum Genomics

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Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes

Cited by 1 publication

References 71 publications

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

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